Newton's Binomium

Thoughts on science, literature, music, food, politics
and anything else I might feel compelled to impose on an unsuspecting public

Tuesday, March 28, 2006

Last laugh

You'll forgive me for returning to this, but the aftershocks haven't finished yet. The Houston Chronicle has nice piece about our paper today, even if I say so myself. (Although I probably would have subtitled it "fuel for selection" or "variation engine". Oh, and did I really split that infinitive at the end?) The author, Patrick Kurp, keeps a very interesting literary blog; for example, check out these posts about Darwin's prose and Fernando Pessoa, written after we talked. (As someone keeps telling me, I should write more about literature myself. I'm thinking something about Borges...)

But today I thought I should write about some not so flattering responses to our paper. A few hours after the paper came out in Nature's website, someone wrote me an email titled "Do you believe in God?" It opened with:

Could sexual relations occur because that is the way God intended to have us populate the earth? [...]

Have you ever asked yourself WHY...God made sexual activity so pleasurable...could it be as a gift to both man and woman?

This could be the easiest evolutionary question ever posed: might it be because individuals who find sex unpleasant have tended to leave fewer descendants? Clearly my fan did not taken the time to actually read the paper. It continues in a crescendo of silliness:

Sometimes people over analyze activities... Is it possible that somethings God just loves you so much that he wants you to exsperience [sic] something greater than yourself... greater than what you can truly describe in words. Something that can't be explained...

I wonder what it's like to be God!

Scary... Think about it: this is what a future biology textbook might say if intelligent design creationists get their way in public schools. I'm amazed at how confidently some people express opinions about things they know so little about.

This is what happens when you put all your eggs in the basket of neo-Darwinism: trying to come up with increasingly risible explanations for the most basic instincts of life. Of course, this explanation is a minority view within the scientific mainstream (for the moment), but it's not that far off a lot of other views on particular processes in the development of life.

I wonder what they've been smoking over there. I'd hate to see what they might consider a serious explanation. Obviously, Pipesman has no idea of what the "scientific mainstream" actually is, which is worrying for a journalist. So let me explain it: I belong to it and your pals over at the Discovery Institute do not.

The origin and maintenance of sex really is one of the big problems of biology; that's not just something we say because it sounds cool. And biologists have been working hard to solve it. Let me illustrate how using some citation analysis. Since 1988, two of the classic books on the subject, John Maynard Smith's Evolution of sex (1978) and Graham Bell's The masterpiece of nature (1982), have been cited by 910 and 693 mainstream scientific papers, according to the ISI Web of Science database. The mutational deterministic hypothesis you seem to find so amusing is actually one of the main players in the field, not some fringe idea. It was proposed almost 20 years ago by Alex Kondrashov in, among others, another paper in Nature. That paper has been cited 381 times. Another major contender for explaining the evolution of sex is contained in this classic paper, which has been cited an even 400 times. To put these numbers in perspective, Darwin's TheDescent of Man has been cited approximately 3000 times over the same period, whereas Dembski's collected works have been cited 84 times. In other words, theories on the evolution of sex have been formulated, analysed, extended, discussed, reviewed, tested and retested in hundreds of papers. That's about as mainstream as it gets.

Wednesday, March 15, 2006

Entanglement

Welcome to all Tangled Bank readers! I thought this would be a good opportunity to write some more about our paper (yes, any excuse!) -- in which I explain how our research came about, and drop a lot of names in the process. The point of this exercise is to cut through the neatness (or "fraud", as Medawar famously put it) of the finished scientific paper, and give a more personal account of how we found what we found.

I met Christina Burch, my collaborator on this project, at the 2004 Evolution meetings in Fort Collins, CO. We had a chat over a beer and found ourselves talking about a paper by Siegal & Bergman which showed that selection for any stable gene expression pattern could lead to greater robustness in whatever specific gene expression pattern a genotype happened to evolve. That paper made a big splash in the robustness field by showing that what we might call classical stabilizing selection was not required for the evolution of robustness. It turns out that Christina had thought more deeply about their paper than I had, and had spotted some things that didn't add up. For example, Siegal & Bergman had incorporated sexual reproduction in their model but did not test for its effect. She'd even ran some preliminary simulations and hadn't been able to replicate all of their original results when she removed sex. We agreed that this was something worth pursuing and that we should try and do some work on it together.

Now such resolutions are common at scientific conferences, but they don't always go anywhere. Scientists constantly get excited about new problems, but they aren't always in a position to take on new projects. In this case, things turned out differently for two reasons. First, I was in the process of completing another project that would soon culminate in a satisfying publication (I was actually working on the resubmission during the meeting), so I was looking for something else to do. One direction I was considering (the next logical step, really) was to connect gene networks to our cell lineage models. When I thought more about it, I thought that the Siegal & Bergman model would be a good way to do that. Second, Rolf Lohaus (on the left in the photo) was about to join my lab to do his PhD. He had visited my lab during the Summer of 2003 while working on his Masters project on a gene network model of C. elegans vulval development, and I thought he would be interested in working on it. I was not disappointed -- Rolf started working on the project as soon as he arrived. Soon, two other students joined the project: Suraj Srinivasan in my lab (on the right in the photo), and Kristen Dang in Christina's lab (whom I have yet to meet in person). The work progressed incredibly quickly (the fastest in our experience), a testament to the quality and commitment of the team we assembled: we submitted a manuscript on it in mid-June 2005.

Let's get back to the science. You might be wondering about what happened to Christina's initial questions about Siegal & Bergman's paper. When I reread it more carefully I agreed with her assessment. What did it for me was the result they showed in Figure 2d -- I couldn't believe that it would be true in asexual populations. When we repeated their simulations we found that we were right on that point -- they had actually missed the effect of sex on the evolution of robustness. However, the main finding of their paper (explained above) was still valid in asexual populations (we show that in our paper, although we present our results in a different way).

So why did we decide to look at directional epistasis and the evolution of sex as well? It turns out that both Christina and I immediately saw the interest of those problems. In her case, this will not surprise you. She had long been interested in directional epistasis, as you can judge from these earlierpapers from her lab. I suppose doing her PhD in Lin Chao's lab must have played a role in that. In my case it won't be so obvious but it's an interesting example of how formative influences can have far reaching consequences.

Although I had never before worked on the evolution of sex, I've been close to people working on it ever since my PhD days, so I've been quite familiar with the field. I started my PhD in Edinburgh, and the closest lab to ours, both intellectually and socially, was that of the theoretician Nick Barton. The reason why that was significant is that, although I didn't interact much with Nick himself, I did interact with people who were interested in the evolution of sex who passed through his lab, such as Joel Peck and Mike Whitlock. Alex Kondrashov, the father of the mutational deterministic hypothesis, also visited for several weeks while I was there and I heard him speak a few times. When I moved to London with my PhD lab, I continued to hear about the evolution of sex from Daniel Falush, then a PhD student in Andrew Pomiankowski's lab. Throughout my postdoc in Armand Leroi's lab (warning: his lab webpage has been frozen in time for 6 years -- I'm still listed as a postdoc there!), the closest lab to ours (Austin Burt's, again both intellectually and socially), was also actively working on the evolution of sex. For example, Matt Goddard, who went on to do an excellent evolution of sex experiment on yeast, did his PhD in Austin's lab.

Which brings us back to our work. When we started looking at the evolution of robustness in sexual and asexual populations, we quickly decided to check the response in directional epistasis. Our thinking on this was also sharpened by the fine papers on Avida and RNA folding -- in fact, we were practically scooped by this paper on Avida. The rest, as happens so often in science, was luck, but as Pasteur pointed out long ago "dans les champs de l'observation le hasard ne favorise que les esprits préparés" ("chance favors the prepared mind").

Friday, March 10, 2006

The way of the dodo...

Yesterday I went over to Rice University to see a screening of Randy Olson's "Flock of Dodos". I was curious to see his "ten things" in practice. I loved it! It was pretty funny at the expense of both sides. Randy managed the rare feat of being incisive [1. intelligently analytical and clear-thinking. 2. accurate and sharply focused] and insightful about intelligent design creationism, without humiliating its proponents (in fact some of them come across quite sympathetically). The scientists were not at their best (the ending is masterful, but I won't spoil it for you), but I found them to be representative of the range of opinions, attitudes and personalities common among my colleagues: from rambly to focused, from introverted to extroverted, from emotional to analytical, etc. I essentially agree with what Carl Zimmer wrote about the movie and, like him, do not want to give too much away and spoil the fun. Just go and watch it!

There was only one problem -- the audience. Apparently the movie has been playing to packed houses in Kansas, Yale, Harvard, etc. Sadly, that was not the case yesterday. I don't know what happened but let's just say that my wife and I, and my four graduate students must have been about 10% of the total. Ironically, there must have been some severe miscommunication on the part of the organizers (not scientists, by the way), because Rice's E&E department first heard about the event a couple of weeks ago when I told Joan Strassmann. After that a couple of emails were sent around, but still I only saw Joan and Dave Queller there (maybe I missed someone else). I have no idea where all the graduate students were -- maybe a free screening isn't enough these days unless there's also free beer and free pizza... If I'd known, I would have offered extra credit to students in my Evolutionary Biology class!

So, the film was excellent, but the discussion afterwards was a bit disappointing. I left before it ended because I was almost fainting from hunger, so I didn't get to congratulate Randy in person as promised. Maybe I can do it the next time he comes to Houston after the movie is released and he becomes famous. Maybe we can even arrange for him to come a give a talk at UH...

Update: "Flock of Dodos" will have it's official World Premiere at Robert De Niro's Tribeca Film Festival on Sunday, April 30 in New York City. Congratulations!

Sunday, March 05, 2006

XXX science

We all knew that sex sells, but it's still fun to see it applied to your own work. Perhaps Randy Olson should add another point to his ten commandments of evolution communication: "make as many references to sex as possible"!

You'll have to excuse the shameless gloating, but I have to highlight some excellent developments:

But don't trust everything you read about our paper... For example, in this piece we learn that we actually did our work with fruitflies. Yes, the experiments shown in Figure 3a/right (µ=0.002) were actually started back in the VIIth century!

Thursday, March 02, 2006

Resistance is not futile

Our paper is out now, so I can finally explain what it's all about. Unfortunately I haven't had much time between grading tests, speaking to journalists and preparing for a talk tomorrow. It remains to be seen how much noise this will make, but I'm pleased with the initial response. Here are some clippings for you:

If you've read the earlier posts, you're probably wondering what robustness could possibly have to do with the evolution of sex? At first it would seem that positive epistasis, where mutations spontaneous mutations have weaker effects in combination than they do separately, is a "many-mutation" version of robustness. However, in the last few years, scientists working on a range of models of biological systems (such as, RNA folding and virus growth) have found that high robustness to mutation (that is, to one mutation) tends to be associated with more negative (or less positive) epistasis. In other words, it seems that selection for high robustness might lead to the evolution of negative epistasis.

So how does robustness to mutation evolve? The obvious answer is that high mutation rates can select for robustness to mutation. This has been known for a while. A less obvious suggestion is that sex might act as a qualitatively similar perturbation to mutation and lead to the evolution of robustness to mutation. To our surprise when we started working on this problem, although this had been predicted (most clearly in an uncharacteristically obscure paper published by Stephen Stearns in a Polish paleontological journal), it had never actually been tested in real organisms or even modelled in any detail.

To explore these questions we took a simple model of a genetic system from the literature. Briefly, it represents a very simple transcriptional regulation gene network. We then looked at the evolution of a very simple phenotype: the ability to produce a stable gene expression pattern. Population of these digital organisms were allowed to evolve such that those that produced stable gene expression patterns survived, while those that produced unstable patterns died. We found that sexually reproducing populations evolved increased robustness to mutations when compared to asexual ones. In addition, negative epistasis evolved in the sexuals, but not the asexuals. In other words, sexual reproduction created the conditions that favor its own perpetuation. If these results hold for real organisms, sex may be self-reinforcing.